Antibody clearance as virulance factor in African sleeping sickness

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Human African trypanosomiasis, commonly known as sleeping sickness, is one of the world’s most neglected infectious diseases. Spread by tsetse flies, trypanosomes not only cause fatal human infection but also the dreaded Nagana, a veterinary malady with dramatic economic consequences. Trypanosomiasis is an exemplary disease of poverty.African trypanosomes are unicellular, flagellate parasites that thrive in the bloodstream of mammals. Evolution has provided the blood parasite with a unique cell surface coat consisting of a single type of variant surface glycoprotein (VSG). We found that in culture, host-derived antibodies are rapidly removed from the VSG coat. The coordinate action of directional cellular motility and plasma membrane recycling is necessary and sufficient for the clearance of host antibodies.The goal of the proposed project is to explore antibody clearance as virulence factor in the course of natural trypanosome infections and to exploit the knowledge gained for novel therapeutic approaches. We have devised a work plan that requires close collaboration between African and German partners. The experimental approach takes advantage of the distinct expertise and resources available in Nairobi and Darmstadt. Advanced molecular cell biology and infection genetics are combined with live animal experiments, epidemiology and bioinformatics. Obviously, the design of our project entails unique challenges and benefits for the young scientist involved.